Anti-CD18 antibody does not block ileal injury induced by phorbol myristate acetate.

Abstract

Acute lung injury (ALI) is frequently complicated by systemic microvascular injury. In previous studies, ALI from acid aspiration resulted in ileal microvascular injury. This was due to systemic inflammation and was prevented by MoAb 60.3, an antibody against the CD18 antigen that mediates leukocyte adherence. The present study was designed to test the hypothesis that ileal microvascular injury during phorbol myristate acetate (PMA)-induced systemic inflammation is also blocked by MoAB 60.3. We assessed the injury by measuring the concentration ratios of lymph protein to plasma protein (i.e., CL/CP) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the CL/CP increased in the ilea of animals given PMA (15 micrograms/kg; n = 5) compared with the ilea of control animals (n = 5) (0.202 +/- 0.024 versus 0.106 +/- 0.010; p = 0.006) and was accompanied by widespread morphologic alterations. Intravenously administering MoAb 60.3 (2 mg/kg) to animals before the PMA infusion (n = 5) yielded a CL/CP value indistinguishable from that of the PMA group (0.222 +/- 0.024 versus 0.202 +/- 0.024; p = NS). These results suggest that CD18-mediated leukocyte adherence is not important in the mechanism of PMA-induced ileal microvascular injury.